Despite the increasing incidence of cardiovascular disease, there are few effective biomaterials currently available for clinical vascular applications. Currently available synthetic biomaterials such as polyethylene terephthalate have a range of vascular applications including endovascular grafting, heart valve replacement, vascular/myocardial patches and vascular closure devices, but it is their poor performance as vascular surgical conduits that exemplifies their deficiencies.
Autologous veins or arteries are preferentially used due to their superior performance and patency, but in at least 30% of patients, these grafts are unavailable due to prior use or disease (Goldman et al., (2004) J. Am. Coll. Cardiol. 44, 2149-56). The early patency of vein graphs can be maximized by the surgeon, though long term failure is unavoidable, resulting mainly from uncontrolled smooth muscle cell proliferation (Fitzgibbon et al., 1996) J. Am. Coll. Cardiol., 28, 616-626). In cases where autologous arterial or venous grafts are unusable or not available, the two leading synthetic materials for both surgical and endovascular implantation are polyethylene terephthalate (DACRON®) and expanded polytetrafluoroethylene (ePTFE). Both polymers perform well in high flow vessels with diameters greater than 6 mm, but neither is suitable for small diameter (less than 4 mm) grafts (Xue and Greisler, 2003) J. Vasc. Sur. 37, 472-80). Both synthetic graft types produce an unfavourable immune response, are highly thrombogenic and do not adequately mimic the compliance of native vessels. Incomplete endothelialization leads to chronic inflammation and hyperplasia (Kannan et al., (2005), J. Biomed. Mate. Res. B Applied Biomaterials, 74, 570-81). This poor performance has been attributed both to the mismatched physical properties of the synthetic graft as well as the intrinsic haemocompatibility of the graft surface (Tai et al., 2000). For example, the tensile strength of Dacron (170-180 MPa) and ePTFE (14 MPa) (Kannan et al., 2005) is substantially greater than those observed for arterial and venous material (1-3 MPa) (Black, (1998) Handbook of biomaterial properties, Springer).
The inadequacy of existing polymeric graft materials has constantly been challenged by the development of new materials, particularly those with more favourable physical properties. An important class of non-biodegradable polymers proposed for vascular graft use are polyurethane elastomers, which exhibit good hemocompatibility and have excellent mechanical properties (Gunatillake et al., (2000) J. App. Poly. Sci. 76, 2026-2040). The wider use of polyurethane biomaterials has been limited, however, by questions surrounding long-term stability of implanted materials. The combined susceptibility of polyurethanes to hydrolysis, cracking, enzymatic degradation, calcification and corrosion to varying degrees depending on the formulation (Santerre et al., (2005), Biomaterials, 26, 7457-70) has led to these doubts regarding biostability and bi-product toxicity. The problems faced by polyurethane biomaterials are common to this field and have prevented any strong competition to DACRON® and ePTFE from emerging. It is clear then, that a large unmet need for a more biocompatible, durable and clinically effective synthetic biomaterial remains.
Elastin has frequently been used in combination with other supporting components. Elastin, digested from animal sources has been combined with gelatin, collagen (Buttafoco et al., (2006) Biomaterials, 27, 724-34) and polymers such as poly(lactide-co-glycolide) (Stitzel et al., (2006) Biomaterials, 27, 1088-94) using electrospinning and producing fibers with improved tensile characteristics. Elastin from porcine arteries has also been used as the scaffold for a graft material, reinforced by physically wrapping the construct with small intestinal submucosa (essentially decellularized collagen) (Hinds et al., (2006) J. Biomed. Mater. Res. Part A, 77, 458-69). Tensile strengths of 1-2 MPa have been reached using these approaches. These materials however, are limited not only by the difficulties associated with the quality and supply of animal elastin but also the likely thrombogenicity of the supporting material.
It is therefore an object of the present invention to provide materials which are suitable for vascular application that are biocompatible and not thrombogenic or having very low thrombogenicity.
It is a further object of the present invention to provide such materials which also have mechanical strength and elasticity that are desirable for vascular applications.